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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11454

Title: Simvastatin Interferes With Process Outgrowth and Branching of Oligodendrocytes
Authors: SMOLDERS, Inge
SMETS, Ilse
Maier, Olaf
vandeVen, Martin
STEELS, Paul
AMELOOT, Marcel
Issue Date: 2010
Publisher: WILEY-LISS
Citation: JOURNAL OF NEUROSCIENCE RESEARCH, 88(15). p. 3361-3375
Abstract: Statins have attracted interest as a treatment option for multiple sclerosis (MS) because of their pleiotropic antiinflammatory and immunomodulatory effects. However, contradictory results have been described when they are applied to oligodendrocytes (OLGs), the cell type predominantly affected in MS. In this study we focus on the in vitro effect of statins on process outgrowth in OLN-93 cells, a well-characterized OLG-derived cell line, and primary cultures of neonatal rat OLGs. Application of the lipophilic simvastatin, as low as 0.1-1 mu M, disturbs process formation of both cell types, leading to less ramified cells. We show that both protein isoprenylation and cholesterol synthesis are required for the normal differentiation of OLGs. It is further demonstrated that the expression of 2',3'-cyclic-nucleotide-3' phosphodiesterase (CNP) and tubulin is lowered, concomitant with a reduction of membrane-bound CNP as well as tubulin. Therefore, we propose that lack of isoprenylation of CNP could help to explain the altered morphological and biochemical differentiation state of treated OLGs. Moreover, expression of specific myelin markers, such as myelin basic protein, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein, was compromised after treatment. We conclude that simvastatin treatment has detrimental effects on OLG process outgrowth, the prior step in (re)myelination, thereby mortgaging long-term healing of MS lesions. (C) 2010 Wiley-Liss, Inc.
Notes: [Smolders, Inge; Smets, Ilse; vandeVen, Martin; Steels, Paul; Ameloot, Marcel] Hasselt Univ, Sch Life Sci, Biomed Res Inst, Diepenbeek, Belgium. [Smolders, Inge; Smets, Ilse; vandeVen, Martin; Steels, Paul; Ameloot, Marcel] Transnat Univ Limburg, Diepenbeek, Belgium. [Smets, Ilse] PHL Univ Coll, Dept PHL Bio, Diepenbeek, Belgium. [Maier, Olaf] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Sect Membrane Cell Biol, A Groningen, Netherlands. [Maier, Olaf] Univ Stuttgart, Inst Cell Biol & Immunol, Stuttgart, Germany.
URI: http://hdl.handle.net/1942/11454
DOI: 10.1002/jor.22490
ISI #: 000283609900015
ISSN: 0360-4012
Category: A1
Type: Journal Contribution
Validation: ecoom, 2011
Appears in Collections: Bio-Physics
Biomedical Research Institute
Physiology

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